tbuckley/cabot-search huggingface dataset:
Gemcitabine and cisplatin plus nivolumab as organ-sparing treatment for muscle-invasive bladder cancer: a phase 2 trial
Authors: Matthew D. Galsky, Siamak Daneshmand, Sudeh Izadmehr, Edgar Gonzalez-Kozlova, Kevin G. Chan, Sara Lewis, Bassam El Achkar, Tanya B. Dorff, Jeremy Paul Cetnar, Brock O. Neil, Anishka D’Souza, Ronac Mamtani, Christos Kyriakopoulos, Tomi Jun, Mahalya Gogerly-Moragoda, Rachel Brody, Hui Xie, Kai Nie, Geoffrey Kelly, Amir Horowitz, Yayoi Kinoshita, Ethan Ellis, Yohei Nose, Giorgio Ioannou, Rafael Cabal, Diane M. Del Valle, G. Kenneth Haines, Li Wang, Kent W. Mouw, Robert M. Samstein, Reza Mehrazin, Nina Bhardwaj, Menggang Yu, Qianqian Zhao, Seunghee Kim-Schulze, Robert Sebra, Jun Zhu, Sacha Gnjatic, John Sfakianos, Sumanta K. Pal
Journal: Nature Medicine (2023)

Abstract Cystectomy is a standard treatment for muscle-invasive bladder cancer (MIBC), but it is life-altering. We initiated a phase 2 study in which patients with MIBC received four cycles of gemcitabine, cisplatin, plus nivolumab followed by clinical restaging. Patients achieving a clinical complete response (cCR) could proceed without cystectomy. The co-primary objectives were to assess the cCR rate and the positive predictive value of cCR for a composite outcome: 2-year metastasis-free survival in patients forgoing immediate cystectomy or &lt;ypT1N0 in patients electing immediate cystectomy. Seventy-six patients were enrolled; of these, 33 achieved a cCR (43%, 95% confidence interval (CI): 32%, 55%), and 32 of 33 who achieved a cCR opted to forgo immediate cystectomy. The positive predictive value of cCR was 0.97 (95% CI: 0.91, 1), meeting the co-primary objective. The most common adverse events were fatigue, anemia, neutropenia and nausea. Somatic alterations in pre-specified genes ( ATM , RB1 , FANCC and ERCC2 ) or increased tumor mutational burden did not improve the positive predictive value of cCR. Exploratory analyses of peripheral blood mass cytometry and soluble protein analytes demonstrated an association between the baseline and on-treatment immune contexture with clinical outcomes. Stringently defined cCR after gemcitabine, cisplatin, plus nivolumab facilitated bladder sparing and warrants further study. ClinicalTrials.gov identifier: NCT03558087 .
Synchronized wearables for the detection of haemodynamic states via electrocardiography and multispectral photoplethysmography
Authors: Daniel Franklin, Andreas Tzavelis, Jong Yoon Lee, Ha Uk Chung, Jacob Trueb, Hany Arafa, Sung Soo Kwak, Ivy Huang, Yiming Liu, Megh Rathod, Jonathan Wu, Haolin Liu, Changsheng Wu, Jay A. Pandit, Faraz S. Ahmad, Patrick M. McCarthy, John A. Rogers
Journal: Nature Biomedical Engineering (2023)
Correction: Predominant expression of Alzheimer’s disease-associated BIN1 in mature oligodendrocytes and localization to white matter tracts
Authors: Pierre De Rossi, Virginie Buggia-Prévot, Benjamin L. L. Clayton, Jared B. Vasquez, Carson van Sanford, Robert J. Andrew, Ruben Lesnick, Alexandra Botté, Carole Deyts, Someya Salem, Eshaan Rao, Richard C. Rice, Angèle Parent, Satyabrata Kar, Brian Popko, Peter Pytel, Steven Estus, Gopal Thinakaran
Journal: Molecular Neurodegeneration (2023)
Define cancer-associated fibroblasts (CAFs) in the tumor microenvironment: new opportunities in cancer immunotherapy and advances in clinical trials
Authors: Hao Zhang, Xinghai Yue, Zhe Chen, Chao Liu, Wantao Wu, Nan Zhang, Zaoqu Liu, Liping Yang, Qing Jiang, Quan Cheng, Peng Luo, Guodong Liu
Journal: Molecular Cancer (2023)

Abstract Despite centuries since the discovery and study of cancer, cancer is still a lethal and intractable health issue worldwide. Cancer-associated fibroblasts (CAFs) have gained much attention as a pivotal component of the tumor microenvironment. The versatility and sophisticated mechanisms of CAFs in facilitating cancer progression have been elucidated extensively, including promoting cancer angiogenesis and metastasis, inducing drug resistance, reshaping the extracellular matrix, and developing an immunosuppressive microenvironment. Owing to their robust tumor-promoting function, CAFs are considered a promising target for oncotherapy. However, CAFs are a highly heterogeneous group of cells. Some subpopulations exert an inhibitory role in tumor growth, which implies that CAF-targeting approaches must be more precise and individualized. This review comprehensively summarize the origin, phenotypical, and functional heterogeneity of CAFs. More importantly, we underscore advances in strategies and clinical trials to target CAF in various cancers, and we also summarize progressions of CAF in cancer immunotherapy.
Tumor‐derived Vimentin as a novel biomarker for distinct subtypes predicting adjuvant chemotherapy resistance and T‐cell‐inflamed phenotype in small cell lung cancer
Authors: Chaoqiang Deng, Yue Wang, Fangqiu Fu, Di Li, Qiang Zheng, Yan Jin, Yuan Li, Haiquan Chen, Yang Zhang
Journal: MedComm (2023)

Abstract Despite recent progress in subtype classification for small cell lung carcinoma (SCLC), little is known about the biomarker for triple‐negative (ASCL1, NEUROD1, and POU2F3 negative) tumors. The long‐term survival, adjuvant chemotherapy (ACT) response, and immune milieu in different SCLC subtypes have also not been well established. Here, we retrospectively collected a large cohort of 192 primary SCLC tumors and reported that ASCL1‐, NEUROD1‐ and POU2F3‐dominant subtypes counted for 61.38%, 19.31%, and 6.21%, respectively. Subtype intra‐tumoral heterogeneity and co‐expression at the single‐cell level existed substantially. The expression of tumor‐derived Vimentin (VIM) was nearly restricted to triple‐negative SCLC tumors (15/19, 78.9%) while YAP1 expression was distributed widely in other subtypes. The SCLC subtyping model was independently prognostic of OS and RFS ( p &lt; 0.001 and p = 0.043). In particular, patients with ASCL1‐positive SCLC tumors can benefit more from ACT, and VIM‐positive tumors did the opposite. Compared with other subtypes, the VIM‐dominant SCLC subtype was associated with abundant but functionally impaired CD4 + and CD8 + T‐cells, which highly expressed inhibitory checkpoints and potentially benefit from PD‐L1 blockade therapy. Our study showed that tumor‐derived SCLC‐V subtype could independently predict ACT response. The distinct immune landscape between subtypes may help inform personalized immune therapeutic approaches.
Ultra‐high static magnetic fields cause immunosuppression through disrupting B‐cell peripheral differentiation and negatively regulating BCR signaling
Authors: Heng Gu, Yufan Fu, Biao Yu, Li Luo, Danqing Kang, Miaomiao Xie, Yukai Jing, Qiuyue Chen, Xin Zhang, Juan Lai, Fei Guan, Huamei Forsman, Junming Shi, Lu Yang, Jiahui Lei, Xingrong Du, Xin Zhang, Chaohong Liu
Journal: MedComm (2023)

To increase the imaging resolution and detection capability, the field strength of static magnetic fields (SMFs) in magnetic resonance imaging (MRI) has significantly increased in the past few decades. However, research on the side effects of high magnetic field is still very inadequate and the effects of SMF above 1 T (Tesla) on B cells have never been reported. Here, we show that 33.0 T ultra-high SMF exposure causes immunosuppression and disrupts B cell differentiation and signaling. 33.0 T SMF treatment resulted in disturbance of B cell peripheral differentiation and antibody secretion and reduced the expression of IgM on B cell membrane, and these might be intensity dependent. In addition, mice exposed to 33.0 T SMF showed inhibition on early activation of B cells, including B cell spreading, B cell receptor clustering and signalosome recruitment, and depression of both positive and negative molecules in the proximal BCR signaling, as well as impaired actin reorganization. Sequencing and gene enrichment analysis showed that SMF stimulation also affects splenic B cells' transcriptome and metabolic pathways. Therefore, in the clinical application of MRI, we should consider the influence of SMF on the immune system and choose the optimal intensity for treatment.
MBE: model-based enrichment estimation and prediction for differential sequencing data
Authors: Akosua Busia, Jennifer Listgarten
Journal: Genome biology (2023)

Abstract Characterizing differences in sequences between two conditions, such as with and without drug exposure, using high-throughput sequencing data is a prevalent problem involving quantifying changes in sequence abundances, and predicting such differences for unobserved sequences. A key shortcoming of current approaches is their extremely limited ability to share information across related but non-identical reads. Consequently, they cannot use sequencing data effectively, nor be directly applied in many settings of interest. We introduce model-based enrichment (MBE) to overcome this shortcoming. We evaluate MBE using both simulated and real data. Overall, MBE improves accuracy compared to current differential analysis methods.
Selected Articles from This Issue
Journal: Clinical Cancer Research (2023)

Highlights| October 02 2023 Selected Articles from This Issue Author & Article Information Online ISSN: 1557-3265 Print ISSN: 1078-0432 ©2023 American Association for Cancer Research2023American Association for Cancer Research Clin Cancer Res (2023) 29 (19): 3827. https://doi.org/10.1158/1078-0432.CCR-29-19-HI Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Article Versions Icon Versions Version of Record October 2 2023 Citation Selected Articles from This Issue. Clin Cancer Res 1 October 2023; 29 (19): 3827. https://doi.org/10.1158/1078-0432.CCR-29-19-HI Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest Search Advanced Search In the past, treatment of patients with hepatocellular carcinoma (HCC) with large tumors or compromised liver function by stereotactic body radiation therapy (SBRT) has been hindered by intolerable toxicity levels and hepatic decline. Individualized therapy, improving the rate of local control while reducing the risk of toxicity, could enhance patient outcomes. In a prospective clinical trial, Herr and colleagues developed a quantitative, utility-based analysis that balances the probability of local tumor control with a patient's probability for treatment-related toxicity to optimize SBRT for HCC with large tumors or impaired liver function. When comparing patients receiving optimized SBRT treatment to patients receiving conventional SBRT by overlap weighting, the optimized SBRT group was found to have equivalent local control and decreased toxicity compared with conventional SBRT. The authors report a 2-year cumulative incidence of local progression of 6.4%, as well as similar one- and two-year freedom from progression rates and overall survival... You do not currently have access to this content.
GenArk: towards a million UCSC genome browsers
Authors: Hiram Clawson, Brian T. Lee, Brian J. Raney, Galt P. Barber, Jonathan Casper, Mark Diekhans, Clay Fischer, Jairo Navarro Gonzalez, Angie S. Hinrichs, Christopher M. Lee, Luis R. Nassar, Gerardo Perez, Brittney Wick, Daniel Schmelter, Matthew L. Speir, Joel Armstrong, Ann S. Zweig, Robert M. Kuhn, Bogdan M. Kirilenko, Michael Hiller, David Haussler, W. James Kent, Maximilian Haeussler
Journal: Genome biology (2023)

Abstract Interactive graphical genome browsers are essential tools in genomics, but they do not contain all the recent genome assemblies. We create Genome Archive (GenArk) collection of UCSC Genome Browsers from NCBI assemblies. Built on our established track hub system, this enables fast visualization of annotations. Assemblies come with gene models, repeat masks, BLAT, and in silico PCR. Users can add annotations via track hubs and custom tracks. We can bulk-import third-party resources, demonstrated with TOGA and Ensembl gene models for hundreds of assemblies. Three thousand two hundred sixty-nine GenArk assemblies are listed at https://hgdownload.soe.ucsc.edu/hubs/ and can be searched for on the Genome Browser gateway page.
Artificial intelligence in diabetes management: Advancements, opportunities, and challenges
Authors: Zhouyu Guan, Huating Li, Ruhan Liu, Chun Cai, Yuexing Liu, Jiajia Li, Xiangning Wang, Shan Huang, Liang Wu, Dan Liu, Shujie Yu, Zheyuan Wang, Jia Shu, Xuhong Hou, Xiaokang Yang, Weiping Jia, Bin Sheng
Journal: Cell Reports Medicine (2023)

The increasing prevalence of diabetes, high avoidable morbidity and mortality due to diabetes and diabetic complications, and related substantial economic burden make diabetes a significant health challenge worldwide. A shortage of diabetes specialists, uneven distribution of medical resources, low adherence to medications, and improper self-management contribute to poor glycemic control in patients with diabetes. Recent advancements in digital health technologies, especially artificial intelligence (AI), provide a significant opportunity to achieve better efficiency in diabetes care, which may diminish the increase in diabetes-related health-care expenditures. Here, we review the recent progress in the application of AI in the management of diabetes and then discuss the opportunities and challenges of AI application in clinical practice. Furthermore, we explore the possibility of combining and expanding upon existing digital health technologies to develop an AI-assisted digital health-care ecosystem that includes the prevention and management of diabetes.
The positive–negative–competence (PNC) model of psychological responses to representations of robots
Authors: Dario Krpan, Jonathan E. Booth, Andreea Damien
Journal: Nature Human Behaviour (2023)

Abstract Robots are becoming an increasingly prominent part of society. Despite their growing importance, there exists no overarching model that synthesizes people’s psychological reactions to robots and identifies what factors shape them. To address this, we created a taxonomy of affective, cognitive and behavioural processes in response to a comprehensive stimulus sample depicting robots from 28 domains of human activity (for example, education, hospitality and industry) and examined its individual difference predictors. Across seven studies that tested 9,274 UK and US participants recruited via online panels, we used a data-driven approach combining qualitative and quantitative techniques to develop the positive–negative–competence model, which categorizes all psychological processes in response to the stimulus sample into three dimensions: positive, negative and competence-related. We also established the main individual difference predictors of these dimensions and examined the mechanisms for each predictor. Overall, this research provides an in-depth understanding of psychological functioning regarding representations of robots.
In planta expression of human polyQ-expanded huntingtin fragment reveals mechanisms to prevent disease-related protein aggregation
Authors: Ernesto Llamas, Seda Koyuncu, Hyun Ju Lee, Markus Wehrmann, Ricardo Gutierrez-Garcia, Nick Dunken, Nyasha Charura, Salvador Torres-Montilla, Elena Schlimgen, Amrei M. Mandel, Erik Boelen Theile, Jan Grossbach, Prerana Wagle, Jan-Wilm Lackmann, Bernhard Schermer, Thomas Benzing, Andreas Beyer, Pablo Pulido, Manuel Rodriguez-Concepcion, Alga Zuccaro, David Vilchez
Journal: Nature Aging (2023)

In humans, aggregation of polyglutamine repeat (polyQ) proteins causes disorders such as Huntington's disease. Although plants express hundreds of polyQ-containing proteins, no pathologies arising from polyQ aggregation have been reported. To investigate this phenomenon, we expressed an aggregation-prone fragment of human huntingtin (HTT) with an expanded polyQ stretch (Q69) in Arabidopsis thaliana plants. In contrast to animal models, we find that Arabidopsis sp. suppresses Q69 aggregation through chloroplast proteostasis. Inhibition of chloroplast proteostasis diminishes the capacity of plants to prevent cytosolic Q69 aggregation. Moreover, endogenous polyQ-containing proteins also aggregate on chloroplast dysfunction. We find that Q69 interacts with the chloroplast stromal processing peptidase (SPP). Synthetic Arabidopsis SPP prevents polyQ-expanded HTT aggregation in human cells. Likewise, ectopic SPP expression in Caenorhabditis elegans reduces neuronal Q67 aggregation and subsequent neurotoxicity. Our findings suggest that synthetic plant proteins, such as SPP, hold therapeutic potential for polyQ disorders and other age-related diseases involving protein aggregation.
Pangenome analysis provides insight into the evolution of the orange subfamily and a key gene for citric acid accumulation in citrus fruits
Authors: Yue Huang, Jiaxian He, Yuantao Xu, Weikang Zheng, Shaohua Wang, Peng Chen, Bin Zeng, Shuizhi Yang, Xiaolin Jiang, Zishuang Liu, Lun Wang, Xia Wang, Shengjun Liu, Zhihao Lu, Ziang Liu, Huiwen Yu, Jianqiang Yue, Junyan Gao, Xianyan Zhou, Chunrui Long, Xiuli Zeng, Yong-Jie Guo, Wen-Fu Zhang, Zongzhou Xie, Chunlong Li, Zhaocheng Ma, Wenbiao Jiao, Fei Zhang, Robert M. Larkin, Robert R. Krueger, Malcolm W. Smith, Ray Ming, Xiuxin Deng, Qiang Xu
Journal: Nature Genetics (2023)
Centuries of genome instability and evolution in soft-shell clam, Mya arenaria, bivalve transmissible neoplasia
Authors: Samuel F. M. Hart, Marisa A. Yonemitsu, Rachael M. Giersch, Fiona E. S. Garrett, Brian F. Beal, Gloria Arriagada, Brian W. Davis, Elaine A. Ostrander, Stephen P. Goff, Michael J. Metzger
Journal: Nature Cancer (2023)

Abstract Transmissible cancers are infectious parasitic clones that metastasize to new hosts, living past the death of the founder animal in which the cancer initiated. We investigated the evolutionary history of a cancer lineage that has spread though the soft-shell clam ( Mya arenaria ) population by assembling a chromosome-scale soft-shell clam reference genome and characterizing somatic mutations in transmissible cancer. We observe high mutation density, widespread copy-number gain, structural rearrangement, loss of heterozygosity, variable telomere lengths, mitochondrial genome expansion and transposable element activity, all indicative of an unstable cancer genome. We also discover a previously unreported mutational signature associated with overexpression of an error-prone polymerase and use this to estimate the lineage to be &gt;200 years old. Our study reveals the ability for an invertebrate cancer lineage to survive for centuries while its genome continues to structurally mutate, likely contributing to the evolution of this lineage as a parasitic cancer.
SIRT2 counteracts primate cardiac aging via deacetylation of STAT3 that silences CDKN2B
Authors: Yanxia Ye, Kuan Yang, Haisong Liu, Yang Yu, Moshi Song, Daoyuan Huang, Jinghui Lei, Yiyuan Zhang, Zunpeng Liu, Qun Chu, Yanling Fan, Sheng Zhang, Yaobin Jing, Concepcion Rodriguez Esteban, Si Wang, Juan Carlos Izpisua Belmonte, Jing Qu, Weiqi Zhang, Guang-Hui Liu
Journal: Nature Aging (2023)
Ex vivo drug response profiling for response and outcome prediction in hematologic malignancies: the prospective non-interventional SMARTrial
Authors: Nora Liebers, Peter-Martin Bruch, Tobias Terzer, Miguel Hernandez-Hernandez, Nagarajan Paramasivam, Donnacha Fitzgerald, Heidi Altmann, Tobias Roider, Carolin Kolb, Mareike Knoll, Angela Lenze, Uwe Platzbecker, Christoph Röllig, Claudia Baldus, Hubert Serve, Martin Bornhäuser, Daniel Hübschmann, Carsten Müller-Tidow, Friedrich Stölzel, Wolfgang Huber, Axel Benner, Thorsten Zenz, Junyan Lu, Sascha Dietrich
Journal: Nature Cancer (2023)

Abstract Ex vivo drug response profiling is a powerful tool to study genotype–drug response associations and is being explored as a tool set for precision medicine in cancer. Here we conducted a prospective non-interventional trial to investigate feasibility of ex vivo drug response profiling for treatment guidance in hematologic malignancies (SMARTrial, NCT03488641 ). The primary endpoint to provide drug response profiling reports within 7 d was met in 91% of all study participants ( N = 80). Secondary endpoint analysis revealed that ex vivo resistance to chemotherapeutic drugs predicted chemotherapy treatment failure in vivo. We confirmed the predictive value of ex vivo response to chemotherapy in a validation cohort of 95 individuals with acute myeloid leukemia treated with daunorubicin and cytarabine. Ex vivo drug response profiles improved ELN-22 risk stratification in individuals with adverse risk. We conclude that ex vivo drug response profiling is clinically feasible and has the potential to predict chemotherapy response in individuals with hematologic malignancies beyond clinically established genetic markers.
Posttransplantation late complications increase over time for patients with SCID: A Primary Immune Deficiency Treatment Consortium (PIDTC) landmark study
Authors: Hesham Eissa, Monica S. Thakar, Ami J. Shah, Brent R. Logan, Linda M. Griffith, Huaying Dong, Roberta E. Parrott, Richard J. O’Reilly, Jasmeen Dara, Neena Kapoor, Lisa Forbes Satter, Sharat Chandra, Malika Kapadia, Shanmuganathan Chandrakasan, Alan Knutsen, Soma C. Jyonouchi, Lyndsay Molinari, Ahmad Rayes, Christen L. Ebens, Pierre Teira, Blachy J. Dávila Saldaña, Lauri M. Burroughs, Sonali Chaudhury, Deepak Chellapandian, Alfred P. Gillio, Fredrick Goldman, Harry L. Malech, Kenneth DeSantes, Geoff D.E. Cuvelier, Jacob Rozmus, Ralph Quinones, Lolie C. Yu, Larisa Broglie, Victor Aquino, Evan Shereck, Theodore B. Moore, Mark T. Vander Lugt, Talal I. Mousallem, Joeseph H. Oved, Morna Dorsey, Hisham Abdel-Azim, Caridad Martinez, Jacob H. Bleesing, Susan Prockop, Donald B. Kohn, Jeffrey J. Bednarski, Jennifer Leiding, Rebecca A. Marsh, Troy Torgerson, Luigi D. Notarangelo, Sung-Yun Pai, Michael A. Pulsipher, Jennifer M. Puck, Christopher C. Dvorak, Elie Haddad, Rebecca H. Buckley, Morton J. Cowan, Jennifer Heimall
Journal: Journal of Allergy and Clinical Immunology (2023)